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Abomasal infusion of branched-chain amino acids or branched-chain keto-acids alter lactation performance and liver triglycerides in fresh cows

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1145-1157页

作者： Kristen Gallagher Isabelle Bernstein Cynthia Collings David Main Ghayyoor Ahmad Sarah Naughton Jayasimha Daddam Vengai Mavangira Mike Vandehaar Zheng Zhou department of Animal Science Michigan State UniversityEast Lansing 48824USA department of Veterinary diagnostic and Production Animal Medicine Ames 50011USA

Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)concentra-tions whereas cows with high circulating BCAA levels have low liver triglyceride(TG).Our objective was to determine the impact of BCAA and their corresponding ketoacids(branched-chain ketoacids,BCKA)on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum.Methods Thirty-six multiparous Holstein cows were used in a randomized block design experiment.Cows were abomasally infused for the first 21 d postpartum with solutions of 1)saline(CON,n=12);2)BCA(67 g valine,50 g leu-cine,and 34 g isoleucine,n=12);and 3)BCK(77 g 2-ketovaline calcium salt,57 g 2-ketoleucine calcium salt,and 39 g 2-ketoisoleucine calcium salt,n=12).All cows received the same diet.Treatment effects were determined using PROC GLIMMIX in SAS.Results No differences were detected for body weight,body condition score,or dry matter intake averaged over the first 21 d postpartum.Cows receiving BCK had significantly lower liver TG concentrations compared to CON(6.60%vs.4.77%,standard error of the mean(SEM)0.49)during the first 3 weeks of lactation.Infusion of BCA increased milk yield(39.5 vs.35.3 kg/d,SEM 1.8),milk fat yield(2.10 vs.1.69 kg/d,SEM 0.08),and lactose yield(2.11 vs.1.67 kg/d,SEM 0.07)compared with CON.Compared to CON,cows receiving BCA had lower plasma glucose(55.0 vs.59.2 mg/dL,SEM 0.86)but higherβ-hydroxybutyrate(9.17 vs.6.00 mg/dL,SEM 0.80).Conclusions Overall,BCAA supplementation in this study improved milk production,whereas BCKA supplementa-tion reduced TG accumulation in the liver of fresh cows.

关键词： Branched-chain amino acids Branched-chain ketoacids Fatty liver Fresh cow

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Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key Laboratory of diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and MCT4.Previous studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug

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Roles of host proteases in the entry of SARS-CoV-2

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Animal Diseases 2024年第1期4卷 27-39页

作者： Alexandria Zabiegalal Yunjeong Kim Kyeong-Ok Chang department of diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State University1800 Denison Avenue ManhattanKS 66506USA

The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.

关键词： SARS-CoV-2 Spike protein(S) Host proteases Cleavage site Virus entry

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Quantitative Assessment of Coronary Flow Reserve by the Variables of Time-Intensity Curve with Myocardial Contrast Echocardiography

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第3期22卷 246-249页

作者：袁霞萍王新房刘望彭康春松 department of diagnostic Ultrasound Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 department of diagnostic Ultrasound the First Hospital Shanxi Medical University Taiyuan 030001

The reliability and reliable indexes of q ua ntitative assessment of coronary flow reserve (CFR) by using time intensity cur ve (TIC) via myocardial contrast echocardiography were investigated. The TIC var iables were obtained by employing acoustic densitometry (AD) technique before an d after acetylcholine (Ach) injection in 12 dogs. Meanwhile, the correlation be tween these variables and CFR was analyzed. Among the variables derived from TIC , peak intensity (PI), area under the curve (AUC) and descending slope (DS) were increased significantly ( P <0.05) with the increase of coronary blood flow a fter Ach injection. Conversely, time to peak (TP), half time of descent (HT) , and mean transit time (MTT) were decreased remarkably ( P <0.0001). Th e P I and AUC ratios from post to pre Ach injection were strongly associated with CFR with the correlation coefficient (r) being 0.8366 and 0.8824, respectively. It is reliable by using the variables derived from TIC with myocardial contrast echocardiography to quantitatively evaluate regional myocardial CFR. The PI an d AUC ratios from post to pre Ach injection are the reliable indexes for quan titative assessment of CFR.

关键词： time intensity curve ultrasound contrast my ocardium variable flow reserve

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Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 251-259页

作者： CHANG Junli ZHAO Fulai SUN Xingyuan MA Xiaoping ZHAO Peng ZHOU Chujie SHI Binhao GU Wenchao WANG Yongjun YANG Yanping Spine Disease Institute Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China department of diagnostic and Interventional Radiology University of TsukubaIbaraki 315-0114Japan

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.METHODS:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry assays.The morphology of cancer cells was observed with inverted phase contrast microscope.The migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell assays.The expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting assay.RESULTS:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma cells.The synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling pathway.CONCLUSION:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

关键词： osteosarcoma tumor necrosis factor-related apoptosis-inducing ligand Wnt signaling pathway beta-catenin polyphyllinⅠ

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Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

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Genes & Diseases 2024年第2期11卷 1050-1065页

作者： Xiaoxuan Wang Lijuan Luo Jingtao Xu Qiuping Lu Haichao Xia Yanran Huang Lulu Zhang Liping Xie Habu Jiwa Shiqiong Liang Xiaoji Luo Jinyong Luo Key Laboratory of diagnostic Medicine Designated By the Chinese Ministry of Education School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400042China

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system.Due to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat BC.Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential.Herein,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular mechanism.We found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC cells.Besides,Ecn had no notable cytotoxicity towards human normal cells.We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells.Remarkably,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells.In summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling pathways.More meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.

关键词： Bladder cancer Combination chemotherapy Echinatin p38 Wnt/β-catenin

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COLOR FLOW IMAGING OF HEPATIC CARCINOMA

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Chinese Journal of Cancer Research 1994年第1期6卷 45-50页

作者： Xu Zhizhang Wang Wenping(department of diagnostic Ultrasound,Zhongshan Hospital,Shanghai Medical University,Shanghai 200032) department of diagnostic Ultrasound Zhongshan Hospital Shanghai Medical University Shanghai

Color flow imaging(CFI)ultrasound technique can discover the tumor vascularity and superimposed it to convontional B-mode ultrasonogram in real-time. The flow velocity on spectral Doppler sonogram can be measured by setting the sample volume to any selected site.One hundred and thirty-six patients with solid hepatic space-occupied lesions had been admitted and 113 cases were confirmed by operation and pathology,23 patients were strongly suspected by hepatic angiography (HAA).Ninety nine patients with 109 nodules were finally diagnosed as hepatic cellular carcinoma(HCC).According to color flow distribution pattern,3 kinds of color configuation had been nominated.Tumor vascularity discovered by CFI,especially the arterial blood flow was easy to be recognized,and its emerge rate was quite different between HCC group(94.5%)and hemangioma(HCH)group(17.07%)(P0. 50 and >0.80 respectively)from HCH (P0.6m/s).The detection rate of A-P shunt was 64% in HCC group,but no case could be detected in HCH group.

关键词： Hepatic carcinoma,Color flow imaging(CFI),Spectral Doppler sonogram,Resistant index(RI),Pulsatile index(PI),Hepatic artery angiography(HAA).

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Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

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World Journal of Gastroenterology 2024年第11期30卷 1636-1643页

作者： Yoshihiro Shibata Hirofumi Ohmura Kazuki Komatsu Kosuke Sagara Atsuji Matsuyama Ryuji Nakano Eishi Baba department of Medical Oncology Fukuoka Wajiro HospitalFukuoka 811-0213Japan department of Oncology and Social Medicine Kyushu University Graduate School of Medical SciencesFukuoka 812-8582Japan department of Pathology and Oncology University of Occupational and Environmental HealthKitakyushu 807-8555Japan department of diagnostic Pathology Fukuoka Wajiro HospitalFukuoka 811-0213Japan

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

关键词： Spindle cell carcinoma Esophagus Myocardial metastasis Epithelial-mesenchymal transition Case report

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Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

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Animal Diseases 2024年第1期4卷 1-18页

作者： Nicholas J.Haley Juergen A.Richt department of Microbiology and Immunology College of Graduate StudiesMidwestern UniversityGlendaleAZUSA department of diagnostic Medicine/Pathobiology College of Veterinary MedicineKansas State UniversityManhattanKSUSA

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

关键词： Prion Bovine Spongiform Encephalopathy Chronic Wasting Disease Transmission Pathogenesis Zoonosis

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Ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 162-169页

作者： Jian Zheng Chun-Feng Li department of diagnostic Radiology Division Harbin Medical University Cancer HospitalHeilongjiangChina department of Gastrointestinal Surgical Ward Harbin Medical University Cancer HospitalHeilongjiangChina

Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cells.RT-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic acid.The expression of invasion-related markers including TP53,CDKN2A,and PTEN was determined.In addition,cell cycle markers including cyclin A,B,D,and E were measured by ELISA.Oxidative stress markers were evaluated using spectrophotometry.Results:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent manner.The expression of BCL-2 was significantly decreased(P0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(P<0.01).Conclusions:Ellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS cells.However,further in vivo and molecular studies are needed to verify its anticancer efficacy.

关键词： Ellagic acid Gastric cancer Apoptosis Autophagy Metastasis Proliferation

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